SPRY4: Sprouty RTK Signaling Antagonist 4
A key regulator of receptor tyrosine kinase signaling, implicated in development and cancer.
Gene Information Card
| Symbol | SPRY4 |
|---|---|
| Full Name | Sprouty RTK Signaling Antagonist 4 |
| Gene Type | protein-coding |
| Chromosomal Location | 5q31.3 |
| NCBI Gene ID | 81848 ncbi.nlm.nih.gov/gene/81848 |
| Ensembl ID | ENSG00000187678 |
| UniProt ID | Q9C004 |
| OMIM ID | 607984 |
| HGNC ID | 15533 |
| Aliases | HHF5, sprouty4 |
Description
SPRY4 encodes a member of the sprouty family of proteins, which function as negative regulators of receptor tyrosine kinase (RTK) signaling pathways, particularly the MAPK/ERK cascade. By inhibiting RTK signaling, SPRY4 modulates cell proliferation, differentiation, and migration. It is involved in embryonic development and its dysregulation is associated with various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Melanoma | Loss of SPRY4 expression leads to increased MAPK signaling, promoting tumor growth and metastasis. | ClinVar, COSMIC |
| Prostate Cancer | Downregulation of SPRY4 is associated with aggressive disease and poor prognosis. | NCBI Gene, PubMed |
| Non-small cell lung cancer | Reduced SPRY4 expression correlates with increased ERK activation and tumor progression. | COSMIC, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | Medium |
| Skin | 8.2 | Medium |
| Prostate | 6.1 | Low |
| Lung | 4.8 | Low |
| Brain | 3.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A549 (lung) | 5.0 | Low expression |
| MCF7 (breast) | 3.5 | Low expression |
| HEK293 (embryonic kidney) | 7.8 | Medium expression |
| SK-MEL-28 (melanoma) | 2.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | missense | <0.1% | Likely loss of function |
| c.214C>T (p.Arg72Trp) | missense | <0.1% | Unknown significance |
| c.463_464insA | frameshift | <0.1% | Loss of function |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations that truncate the protein or prevent translation are classified as loss-of-function.
Gain of Function (GOF)
No gain-of-function mutations have been reported in SPRY4.
Dominant Negative (DN)
No dominant-negative mutations have been characterized for SPRY4.
View complete mutation data：
Gene Ontology (GO)
| • negative regulation of ERK1 and ERK2 cascade | • regulation of signal transduction |
| • cell migration | • cell proliferation |
| • protein binding |
Pathways
• MAPK signaling pathway
• RTK signaling
• FGF signaling pathway
Protein Summary
SPRY4 is a 300-amino acid protein containing a conserved cysteine-rich domain (sprouty domain) that mediates its interaction with signaling molecules. It localizes to the cytoplasm and membrane, where it inhibits RTK signaling by binding to components of the MAPK cascade, such as Raf and MEK. The protein is involved in branching morphogenesis and organogenesis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SPRY4 Knockout HEK293 Cell Line | EDJ-KQ9755 | Human | 81848 | Details Get a Quote |
| SPRY4 Knockout A-549 Cell Line | EDJ-KQ36580 | Human | 81848 | Details Get a Quote |
| SPRY4 Knockout HCT 116 Cell Line | EDJ-KQ36581 | Human | 81848 | Details Get a Quote |
| SPRY4 Knockout HeLa Cell Line | EDJ-KQ57418 | Human | 81848 | Details Get a Quote |
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